Healthy Volunteers
Conditions
Brief summary
A Phase 1b/2a, Randomized, Multi-Center, Open-Label, Fixed-Sequence Study to Evaluate the Effect of Oral SYN-004 on the Pharmacokinetics of Intravenous Ceftriaxone in Healthy Adult Subjects with a Functioning Ileostomy.
Detailed description
This is a Phase 1b/2a, randomized, multi-center, open-label study. Twenty otherwise healthy subjects between the ages of 18 and 80 years, inclusive, with functioning ileostomies were planned to be enrolled. In the first treatment period (Period 1) all subjects received an IV infusion of 1 g ceftriaxone. Subjects had a 3 - 7 day washout period between Period 1 and Period 2. In the second treatment period (Period 2) all subjects received an IV infusion of 1 g ceftriaxone and 2 oral doses of either 75 or 150 mg of SYN-004, according to the randomization schedule, which were administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion.
Interventions
DRUGPeriod 1 - Treatment Sequence AB
Period 1: Ceftriaxone 1 g infused IV over 30 minutes only, no SYN-004
DRUGPeriod 1 - Treatment Sequence AC
Period 1: Ceftriaxone 1 g infused IV over 30 minutes only, no SYN-004
DRUGPeriod 2 - Treatment Sequence AB
Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 75 mg
DRUGPeriod 2 - Treatment Sequence AC
Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 150 mg
Sponsors
Theriva Biologics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. The subject has a functioning ileostomy which has been in place for \> 3 months. 2. Male or female between the ages of 18 and 70 years, inclusive. 3. Other than a functioning ileostomy, the subject is free from clinically significant illnesses or disease.
Exclusion criteria
1. Subjects who have active hepatic, small intestine, or biliary tract disease. 2. Subjects who have active ulcerative colitis, Crohn's disease, other inflammatory bowel disease. 3. Subjects with known malignancy requiring treatment \< 6 months prior to study screening. 4. Subjects who have, in the opinion of the investigator, significant concurrent medical illness. 5. Subjects who are currently taking concomitant medications which may interfere with study evaluation. 6. Subjects who have received an investigational drug within 30 days or within a time period consistent with a washout period of 5 half-lives, whichever is longer, of the first dose of ceftriaxone. 7. Subjects with a known history of allergy to any cephalosporin, penicillin or any β-lactam antibiotic. 8. Subjects who have known active malabsorption syndromes(s) that, in the judgment of the investigator, could compromise the objectives of the study. 9. Subjects who have used any oral, intramuscular, or IV anti-microbial medication during the last 3 weeks prior to the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004. | 2 weeks | — |
| Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004. | 2 weeks | Samples were collected at 0.25 h, 0.5 through 2 h, and 3 through 7 h after the infusion start. Standard deviations may be 0 if all collected T max values occur at the same time. |
| Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004. | 2 weeks | — |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose 1 g ceftriaxone and two low doses of SYN-004 | 6 |
| High Dose 1 g ceftriaxone and two high doses of SYN-004 | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1- Ceftriaxone Without SYN-004 | AE w/ ceftriaxone, not dosed w/ IP | 1 | 0 |
Baseline characteristics
| Characteristic | Low Dose | High Dose | Total |
|---|---|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 11.9 | 57.1 years STANDARD_DEVIATION 11.6 | 48.5 years STANDARD_DEVIATION 13.8 |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 4 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Sequence AB | Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004. | Period 1 | 464,400.0 h*ng/mL |
| Treatment Sequence AB | Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004. | Period 2 | 478,800.0 h*ng/mL |
| Treatment Sequence AC | Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004. | Period 1 | 656,200.0 h*ng/mL |
| Treatment Sequence AC | Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004. | Period 2 | 643,800.0 h*ng/mL |
Primary
Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Sequence AB | Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004. | Period 1 | 137,800.0 ng/mL |
| Treatment Sequence AB | Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004. | Period 2 | 143,800.0 ng/mL |
| Treatment Sequence AC | Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004. | Period 1 | 178,600.0 ng/mL |
| Treatment Sequence AC | Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004. | Period 2 | 169,200.0 ng/mL |
Primary
Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004.
Samples were collected at 0.25 h, 0.5 through 2 h, and 3 through 7 h after the infusion start. Standard deviations may be 0 if all collected T max values occur at the same time.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Sequence AB | Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004. | Period 1 | 0.5 hours | Standard Deviation 0 |
| Treatment Sequence AB | Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004. | Period 2 | 0.5 hours | Standard Deviation 0 |
| Treatment Sequence AC | Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004. | Period 2 | 0.5 hours | Standard Deviation 0 |
| Treatment Sequence AC | Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004. | Period 1 | 0.5 hours | Standard Deviation 0 |